Our general research objectives are to continue our studies on the mechanisms of pathologic effects produced by ethanol. Studies will be conducted by integrated biochemical and structural techniques, in rats and baboons (both in vivo and in vitro), to elucidate further the effects of ethanol on lipid and intermediary metabolism in liver, heart and kidney. A special attempt will be made at assessing the effect of chronic ethanol feeding on the capacity of liver mitochondria to oxidize fatty acids, and the associated production of ketones. The role of possible changes of hepatic lipase activity in the pathogenesis of the ethanol induced fatty liver will be studied. Investigations will be carried out on the effect of ethanol on glycerol metabolism in the liver. The effects of chronic ethanol intake on lipoprotein metabolism will be determined after the development of a technique for the chronic administration of large amounts of ethanol. A number of metabolic, pharmacologic and biochemical changes attributable to chronic ethanol ingestion will be defined including differences in rates of ethanol metabolism, total body energy metabolism, the state of reduction of hepatic pyridine nucleotides and coupled metabolites, activity of liver acetaldehyde and potentiation of the effects of hepatotoxic agents. The amount, type and origin of the lipid accumulated in heart and kidney after chronic ethanol consumption will also be determined. The immediate objectives are to elucidate the pathogenesis of complications of alcoholism in liver and other tissues and to define the biochemical differences between alcoholics and non-alcoholics. The ultimate goal is the application of this knowledge to the successful prevention and treatment of alcohol related diseases, especially those affecting the liver and intermediary metabolism. Bibliographic references: Korsten, M.A., Matsuzaki, S., Feinman, L. and Lieber, C.S. High blood acetaldehyde levels following ethanol administration: Differences between alcoholic and non-alcoholic subjects. New Eng. J. Med. 292:386-389, 1975; Lieber, C.S., DeCarli, L.M. and Rubin, E. Sequential production of fatty liver, hepatitis and cirrhosis in sub-human primates fed ethanol with adequate diets. Proc. Nat. Acad. Sci. USA 72:437-441, 1975.